Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease.
In neurons, cytoplasmic dynein functions as a molecular motor responsible for retrograde axonal transport. An impairment of axonal transport is thought to play a key role in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis, the most frequent motor neuron disease in the elderly. In this regard, previous studies described two heterozygous mouse strains bearing missense point mutations in the dynein heavy chain 1 gene that were reported to display late-onset progressive motor neuron degeneration. Here we show, however, that one of these mutant strains, the so-called Cra mice does not suffer from motor neuron loss, even in aged animals. Consistently, we did not observe electrophysiological or biochemical signs of muscle denervation, indicative of motor neuron disease. The "hindlimb clasping" phenotype of Cra mice could rather be due to the prominent degeneration of sensory neurons associated with a loss of muscle spindles. Altogether, these findings show that dynein heavy chain mutation triggers sensory neuropathy rather than motor neuron disease.
Dupuis
Luc
L
INSERM, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, F-67085, France. ldupuis@neurochem.u-strasbg.fr
Fergani
Anissa
A
Braunstein
Kerstin E
KE
Eschbach
Judith
J
Holl
Nathalie
N
Rene
Frédérique
F
Gonzalez De Aguilar
Jose-Luis
JL
Zoerner
Björn
B
Schwalenstocker
Birgit
B
Ludolph
Albert C
AC
Loeffler
Jean-Philippe
JP
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001572:Benzofurans; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D056445:Cytoplasmic Dyneins; D004195:Disease Models, Animal; D004398:Dyneins / Q000235:genetics*; D004576:Electromyography / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016472:Motor Neuron Disease / Q000235:genetics / Q000503:physiopathology; D009046:Motor Neurons / Q000473:pathology; D009121:Muscle Denervation / Q000379:methods; D018482:Muscle, Skeletal / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D009469:Neuromuscular Junction / Q000473:pathology; D012678:Sensation Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D013126:Spinal Nerve Roots / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D001572:Benzofurans; C516947:Dync1h1 protein, mouse; C038675:true blue; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002795:Choline O-Acetyltransferase; D056445:Cytoplasmic Dyneins; D004398:Dyneins